Angèle Gayet-Ageron1, Thomas Agoritsas2, Sandrine Rudaz3, Delphine Courvoisier3, Thomas Perneger3. 1. Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland. Electronic address: angele.gayet-ageron@hcuge.ch. 2. Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland; Department of Clinical Epidemiology & Biostatistics, Faculty of Health Science, McMaster University, 1280 Main St. W. Hamilton, Ontario, Canada L8S 4K1. 3. Division of Clinical Epidemiology, University Hospitals of Geneva and Faculty of Medicine, 6 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland.
Abstract
OBJECTIVES: To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial. STUDY DESIGN AND SETTING: We conducted an experimental survey among corresponding authors of randomized controlled trials indexed in MEDLINE. We described two hypothetical studies and asked the respondents' opinion on the largest loss of effectiveness that is clinically negligible (or the smallest lost of effectiveness that is clinically important in the superiority scenario). We randomly manipulated four study attributes in each vignette, using a factorial design. RESULTS: A total of 364 researchers participated. The values for NIMs were significantly lower than the differences to be detected in a superiority trial. The NIM was smaller when the primary outcome was mortality compared with treatment failure, when baseline risk in the control arm was lower, and when the advantage of the new treatment was a lower cost compared with having fewer side effects. In contrast, the population age group under study and the difficulty to recruit patients showed no effect on the choice of the NIM. CONCLUSION: In our experimental study, the factors associated with lower NIMs were mortality as a primary outcome, low baseline risk, and a less costly new treatment.
OBJECTIVES: To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial. STUDY DESIGN AND SETTING: We conducted an experimental survey among corresponding authors of randomized controlled trials indexed in MEDLINE. We described two hypothetical studies and asked the respondents' opinion on the largest loss of effectiveness that is clinically negligible (or the smallest lost of effectiveness that is clinically important in the superiority scenario). We randomly manipulated four study attributes in each vignette, using a factorial design. RESULTS: A total of 364 researchers participated. The values for NIMs were significantly lower than the differences to be detected in a superiority trial. The NIM was smaller when the primary outcome was mortality compared with treatment failure, when baseline risk in the control arm was lower, and when the advantage of the new treatment was a lower cost compared with having fewer side effects. In contrast, the population age group under study and the difficulty to recruit patients showed no effect on the choice of the NIM. CONCLUSION: In our experimental study, the factors associated with lower NIMs were mortality as a primary outcome, low baseline risk, and a less costly new treatment.
Authors: Sandra Pong; Robert A Fowler; Nicholas Mitsakakis; Srinivas Murthy; Jeffrey M Pernica; Elaine Gilfoyle; Asha Bowen; Patricia Fontela; Winnie Seto; Michelle Science; James S Hutchison; Philippe Jouvet; Asgar Rishu; Nick Daneman Journal: Med Decis Making Date: 2022-05-18 Impact factor: 2.749